Treating Bipolar Depression: Psychiatry is Changing

Yesterday, after a deliberate sabbatical, I put out my first Newsletter of the year. The theme was "treating bipolar depression." To briefly recap:

In 2001, at the Fifth International Conference on Bipolar Disorder, Robert Post MD, then of the NIMH, surprised his audience by revealing study findings that showed bipolar patients are depressed three times more often than they are manic or hypomanic.

At the time, despite little or no evidence to support it, few clinicians questioned the standard practice of treating bipolar depression with a mood stabilizer-antidepressant cocktail.

Seven years later, in May this year at the American Psychiatric Association's annual meeting, Dr Post advised his audience: "We have to change the way we practice this illness."

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Dr Post was commenting on studies from STEP-BD, a series of large scale real world clinical trials underwritten by the NIMH. At the same APA symposium, Gary Sachs MD of Harvard, who headed up STEP-BD, reported the findings relating to treating bipolar depression:

The first study found that depressed bipolar patients fared no better on an antidepressant with a mood stabilizer than with a mood stabilizer alone. The study measured for "durable recovery," eight weeks in remission, a much higher standard than industry-sponsored trials. About a quarter of the patients in both groups achieved durable recovery. In other words, adding an antidepressant produced no benefit.

The surprise was that patients did not get worse on an antidepressant, but two later findings added strong caveats to this:

One study involved a group of bipolar patients whose depressions were complicated by some manic features. These and other "mixed states" are fairly common in bipolar, more so than the "pure" depressions and manias that get all the attention. The DSM-IV recognizes only full-blown depression with full-blown mania, but STEP-BD found that even just two manic features in depression can have a significant clinical impact. Those with mixed depressions experienced worsened mania symptoms with an antidepressant added to their mood stabilizer.

The authors of this study cautioned that clinicians who fail to pick up manic symptoms in their patients' depressions may mistakenly overestimate the benefits of an antidepressant.

Another study found that patients who rapid-cycled experienced more mood episodes on an added antidepressant over one year.

A 2003 study by Lori Altshuler MD of UCLA found that about 15 percent of bipolars may benefit from being left on an antidepressant, but STEO-BD failed to tease out this population.

STEP-BD also found patients on three forms of talking therapy (cognitive-behavioral therapy, interpersonal social rhythm therapy, and family-focussed therapy) added to their meds got better 110 days quicker. These therapies are aimed at helping patients (and family members) cope with the challenges of the here and now.

In another APA symposium, Robert Hirschfeld MD of the University of Texas at Galveston outlined what we are likely to see when the APA publishes its Revised Bipolar Treatment Guidelines in May next year. For bipolar depression, these include:

Acute (initial) phase: Seroquel (very strong supporting evidence for bipolar depression). Dr Hirschfeld noted that of six clinical trials for Lamictal, only one resulted in the drug faring better than the placebo. Therefore, the APA won't be recommending the drug as first line treatment for acute bipolar depression. As an add-on, he said, it is better.

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Maintenance (long term) phase: Lamictal has more evidence for long-term treatment. Also looking good is talking therapy.

Summing Up

As a general rule, the evidence shows that for treating bipolar depression, adding an antidepressant to a mood stabilizer is not advisable. The experts do acknowledge that you may be an exception to this rule.

With regard to other meds and therapies, the evidence reveals there is precious little evidence. Our clinicians, by and large, are still flying in the dark. As Dr Post at the APA symposium advised: